Since the discovery of macrophages in adipose tissue, many laboratories have focused their effort on understanding the contribution of these immune cells to metabolic diseases. Despite great progress in characterizing obesity as a state of low-grade inflammation, very little is known about the multiple phenotypes and functions of macrophages in metabolic tissues. The lack of methods to carefully investigate cell-to-cell variability in macrophage phenotype and to manipulate gene expression in a cell-specific manner has delayed answering these crucial questions. Our lab takes advantage of sophisticated methods, such as next generation sequencing, CytOF and gene silencing in a cell specific manner, to investigate macrophage subpopulations and their function in obesity-associated metabolic complications.